Ultrastructural Characterization of Zika Virus Replication Factories.

Mirko Cortese (1) , Sarah Goellner (1) , Eliana Gisela Acosta (1) , Christopher John Neufeldt (1) , Olga Oleksiuk (1) , Marko Lampe (2) , Uta Haselmann (1) , Charlotta Funaya (3) , Nicole Schieber (4) , Paolo Ronchi (2) , Martin Schorb (2) , Priit Pruunsild (5) , Yannick Schwab (2, 4) , Laurent Chatel-Chaix (6, 1) , Alessia Ruggieri (1) , Ralf Bartenschlager (1, 7)

1 Department of Infectious Diseases, Molecular Virology
2 EMBL - European Molecular Biology Laboratory [Heidelberg]
3 Electron Microscopy Core Facility
4 Cell Biology and Biophysics Unit
5 Interdisciplinary Center for Neurosciences (IZN)
6 INRS-IAF - Institut Armand Frappier
7 DZIF - German Center for Infection Research

A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.

Keywords: Zika virus; electron microscopy; electron tomography; flavivirus; human neural progenitor cells; intermediate filaments; live-cell imaging; microtubules; replication factories; replication organelles

Domains: Life Sciences [q-bio]

Mirko Cortese, Sarah Goellner, Eliana Gisela Acosta, Christopher John Neufeldt, Olga Oleksiuk, et al.. Ultrastructural Characterization of Zika Virus Replication Factories.. Cell Reports, 2017, 18 (9), pp.2113-2123. ⟨10.1016/j.celrep.2017.02.014⟩. ⟨pasteur-01535196⟩